Method for testing peritoneal function

ABSTRACT

The peritoneal function of a peritoneal dialysis patient is examined to evaluate the condition of the patient. An examining method comprises a step of alternately repeating introduction/drainage of a predetermined quantity of a peritoneal dialyzing fluid of an osmotic pressure and introduction/drainage of a predetermined quantity of another peritoneal dialyzing fluid of an osmotic pressure different from the former one, a step of examining the drain to determine the quantity of peritoneal dialyzing fluid staying in the abdominal cavity of the patient and the concentration of a solute of interest, a step of conducting a peritoneal equilibrium test, and a step of conducting a blood test to grasp the change of the state of the blood caused by the introduction and drainage. The blood test step is executed only once. The current states of the peritoneal dialysis capability and the water removal capability of the patient can be efficiently and accurately evaluated so as to carry out peritoneal dialysis most suitable for the condition of the patient.

TECHNICAL FIELD

The present invention relates to a method for testing peritonealdialysis function and water removal function, so as to evaluateefficiently and accurately the current state of the peritoneal functionin patients with chronic renal failure, in order to perform a peritonealdialysis that is optimal for the condition of that patient.

BACKGROUND ART

One of the most important issues in conventional medical treatment ofperitoneal dialysis has been how to correctly determine the peritonealdialysis state and the peritoneal permeability of peritoneal dialysispatients so as to evaluate the peritoneal function and determine theoptimum dialysis conditions. For example, with Continuous AmbulatoryPeritoneal Dialysis (CAPD), which is a so-called chronic peritonealdialysis treatment that was proposed in the 1970s, approximately twoliters of peritoneal dialysis fluid is retained within the abdominalcavity for five to six hours, and is exchanged from four to six timesdaily. Also, to maintain constancy within the patient's body, thedialysis function and water removal function (hereinafter, collectivelyreferred to as “peritoneal function”) of the patient's peritoneum isevaluated, and the most suitable dialysis fluid exchange schedule(hereinafter, referred to as “dose”) based on that evaluation is set.

However, during the 1970s, which is when CAPD was proposed, very littlewas known of the characteristics of peritoneal function and the changeover time in peritoneal function over the course of peritoneal dialysis,and thus there was no established testing method for appropriatelyevaluating peritoneal function, and the dose was set based on physicianexperience and judgment.

By the 1980s, as the number of clinical cases increased, it became clearthat peritoneal function differed for each patient, and methods fortesting peritoneal function involving qualitative evaluation of dialysisfunction and water removal function were proposed. PeritonealEquilibrium Test (hereinafter, also referred to as “PET”) is one of themost frequently used qualitative evaluation methods. With PET,peritoneal function is divided into four categories, these being good,moderately good, moderately poor, and poor, and a general dose patternthat is considered appropriate is proposed for each category.

By the 1990s, it was shown that there are limitations to the patientsfor which qualitative evaluation methods may be adopted, andquantitative evaluation methods that take patient body type into accountwere proposed. The quantitative evaluation method uses creatinineclearance, which is one index for the dialysis amount of chronicperitoneal dialysis patients, urea Kt/V, and statistical results onsurvival rates, as criteria. The dose that satisfies the quantitativecriteria of these two parameters with respect to survival rate is judgedto be the optimum dosage. By using the above qualitative evaluationmethod and this quantitative evaluation in tandem, it became possible todetermine the optimum dose pattern and dose.

The use of these two evaluation methods in tandem, however, at mostresults in only an evaluation of the suitability of a dose at variouspoints. Consequently, the setting of the dose was performed by trial anderror, and there was the problem that the physician had only hisexperience to rely on when setting a dose.

Accordingly, a computer simulation that builds a mathematical model ofchronic peritoneal dialysis methods and proposes the most suitable dosebased on analysis of the speed at which the peritoneum moves substanceswas proposed. Using computer simulation made it possible to propose adose suited for the peritoneal function of the patient by adopting boththe dose pattern proposed by qualitative evaluation and the criteriaindicated by quantitative evaluation.

However, there was no effective and economical clinical data collectionprotocol (testing method) for collecting the data necessary for thisanalysis. Although numerous clinical data collection protocols (testingmethods) for implementing computer simulation have been proposed, eachof the methods takes the body's circadian rhythm into consideration andmeasures the material balance of monitored solutes (such as urinetoxins) and the uptake and release of water over a 24-hour period.

FIG. 1 shows an example of the procedure of a conventional method fortesting peritoneal function. The horizontal axis shows the time elapsedfrom the start of testing. “Fluid infusion” and “fluid drain” inaccordance with the passage of time are shown. Also, the timing of abody weight measurement 11, a blood draw 12, a urine storage 13, and aurine test 14 are shown in relation to “fluid infusion” and “fluiddrain.”

As shown in FIG. 1, to detect the material balance of monitored solutes(such as urine toxins) and the uptake and release of water over a24-hour period, first, infusion of a low osmotic pressure fluid (360(units are m0sm/kg-solvent; same below)), which is a dialysis fluidhaving a low osmotic pressure, is begun in the evening (22:30) two daysprior to the day on which testing is finished. The next morning thefluid is drained and a first blood sample 12 (8:00) is taken.

Next, a body weight measurement 11 is performed, and then a mediumosmotic fluid (400), which is a dialysis fluid having a high osmoticpressure, is infused, and for the peritoneal equilibrium test (PET), thefluid is drained, some is sampled, and then is returned two times atpredetermined time intervals, after which the fluid is finally drained.It should be noted that in general PET is performed using a mediumosmotic pressure fluid (400). Also, PET is a test that should beperformed in the hospital, and the second blood sample 12 is generallytaken while the patient is in the hospital. After that the dialysisfluid is infused and drained, and when the final fluid drain is complete(8:00), a third blood sample 12 is taken and a urine test 14 isperformed.

In this testing procedure, the patient was forced to stay in thehospital because it was necessary to take a blood sample and perform aPET. In other words, in the above test, several blood samples are takenduring a 24-hour period. It was therefore frequently necessary to admitpatients to the hospital, depending on their living environment, andthis was a problem because it imposed time constraints on patients andleft them mentally fatigued.

There was also the problem that the large number of tests placed a largetime and work burden on the patient and medical staff, and in spite ofthis, it was difficult to gather data that accurately reflected thenormal daily condition of the patient.

DISCLOSURE OF THE INVENTION

The object of the present invention is to provide a method for testingperitoneal function with which it is possible to efficiently andaccurately evaluate the current condition of the peritoneal dialysisfunction and the water removal function of a patient, such thatperitoneal dialysis that is optimal for the condition of the patient isperformed.

A testing method of the present invention is a method for testingperitoneal function in order to evaluate a condition of a peritonealdialysis patient, and includes the steps of: repeatedly performing afluid infusion and a fluid drain of a predetermined amount of peritonealdialysis fluid in alternation for peritoneal dialysis fluids havingdifferent osmotic pressures; analyzing the drain fluid in order toassess an amount of the peritoneal dialysis fluid that is retainedwithin the abdominal cavity of a patient, and a concentration ofmonitored solutes in the peritoneal dialysis fluid; performing aperitoneal equilibrium test; and performing a blood test in order toassess a change in condition in the blood due to performing the fluidinfusion and fluid drain, wherein the step of performing a blood test isexecuted only once.

BRIEF DESCRIPTION OF DRAWINGS

FIG. 1 is a diagram showing the procedure of a conventional example of amethod for testing peritoneal function.

FIG. 2 is a diagram showing the procedure of the method for testingperitoneal function according to an embodiment of the present invention.

FIG. 3 is a diagram showing the change in blood colloid concentrationwith respect to test time.

FIG. 4 is a diagram showing the change in blood crystalloidconcentration with respect to test time.

FIG. 5 is a diagram showing the change in blood electrolyteconcentration with respect to test time.

FIG. 6 is a diagram showing the relationship between the amount ofdialysis fluid within the abdominal cavity and dwell time.

FIG. 7 is a diagram showing the relationship between soluteconcentration and dwell time.

BEST MODE FOR CARRYING OUT THE INVENTION

The testing method of the present invention requires a blood test asingle time only, allowing the economic and mental burden that the testimposes on patients and the sense of time constraint to be reduced. Themethod is based on the finding that there is very little change in theblood solute concentration of chronic peritoneal dialysis patientsduring the 24-hour test period. As a result, a simple testing methodthat uses test data from a blood sample taken at a representative timeduring a 24-hour period and that substantially does not affect theprecision of analysis by computer simulation was achieved.

In this testing method, it is preferable that the peritoneal equilibriumtest is performed last of all the steps, and the blood test is performedimmediately before or immediately after the peritoneal equilibrium test,or is performed during the peritoneal equilibrium test. Thus, by takinga single blood sample during testing, preferably when testing hasfinished, along with a peritoneal equilibrium test, which is aqualitative evaluation method, it is possible to minimize the amount oftime spent in the hospital for the purpose of testing.

It is preferable that the monitored solutes for assessing peritonealfunction are total protein, albumin, glucose, creatinine, urea, sodium,and chlorine.

It is also preferable that the albumin concentration of the drain fluidis extrapolated based on the total protein concentration of the drainfluid. Thus, the measurement expenses can be kept even lower.

It is preferable that the step of repeating fluid infusion and fluiddrain is performed at least three times for each dialysis fluid ofrespective osmotic pressure. In this case, it is preferable that whenthe step of repeating fluid infusion and fluid drain is performed aplurality of times using dialysis fluid having the same osmoticpressure, then a dwell time from when the dialysis fluid is infuseduntil when the dialysis fluid is drained is different each time.

With this method, when the change over time in the water removal amountand the change over time in the solute concentration of the drain fluidare expressed as curved lines based on three types of clinical data fordifferent dwell times, it is possible to precisely perform curve fittingfor the following reason. That is, this is because in order to perform ahigh-precision curve fitting it is necessary to predict more preciselythe time period during which there is a large change in the curved line,and by setting a large number of test sampling points in the time periodwhere change is largest due to the change over time in the water removalamount, that is, the time period in which the water removal amount islargest, there is better precision of curve fitting. As a result, aperitoneal dialysis simulation, such as one that includes dwell times inwhich curve fitting is not performed when setting the dose, becomespossible.

Methods for testing peritoneal function according to embodiments of thepresent invention are described below with reference to the drawings.FIG. 2 shows the procedure of a method for testing peritoneal functionaccording to the present embodiment. FIG. 2, like FIG. 1, shows thetiming for “fluid infusion” and “fluid drain” as time elapses. Thetiming of a body weight measurement 21, a blood draw 22, a urine storage23, and a urine test 24 are shown in relation to “fluid infusion” and“fluid drain.”

Because in the testing method of the present embodiment as well it isnecessary to detect the substance balance of monitored solutes (such asurine toxins) and the uptake and drain of water over a 24-hour period,the infusion of dialysis fluid is started from the evening two daysprior to the day on which testing ends. However, in the presentembodiment, 2L of high osmotic pressure dialysis fluid, that is, themedium osmotic fluid (400), are infused before testing is begun. This isbecause by infusing a dialysis fluid with high osmotic pressure it ispossible to ensure a long dwell time. By contrast, when a low osmoticpressure fluid (360) is infused when testing is started, the dwell timeis short, and this requires fluid infusion and fluid drain to beperformed during the night and affects the lifestyle of the patient.

The present testing method also differs from the conventional testingmethod in that the first blood sample is not taken at the point thatfluid drain is performed the following morning. Then, infusion of 2L oflow osmotic pressure fluid (360) is performed twice, after which 2L ofmedium osmotic pressure fluid (400) and low osmotic pressure fluid (360)are infused and drained in alternation, and a single blood sample 22 istaken prior to starting the final fluid infusion. Simultaneously, aurine sample is obtained from patients with urine for the urine test 24,and for this reason urine is retained 23. Lastly, a body weightmeasurement 21 is performed, and then a peritoneal equilibrium test(PET) is performed. In other words, the dialysis fluid that is infusedis collected over three collections, and then the entire test is ended.

In this manner, the testing method of the present embodiment ischaracterized in that the timing and the number of the blood samplestaken is different from the conventional method. The reason why thischange is possible is explained through the following demonstrationexperiment.

First, approximately 100 chronic peritoneal dialysis patients weretested using the conventional method for testing peritoneal functionshown in FIG. 1, in which blood samples are taken and drained dialysisfluid is stored over a 24-hour period to measure the concentration ofmonitored solutes in blood and drained fluid during testing. As for thedialysis fluid exchange schedule of the testing, two types of dialysisfluid (low osmotic pressure fluid and medium osmotic pressure fluid)having different osmotic pressures that are adopted based on waterremoval capability, were each held three times, and each dwell time wasdifferent. The reason for doing this is to prevent drops in theprecision of analysis by computer simulation and to increase variationin the dosage simulation.

Preferable examples of the monitored solutes that are important forconfirming the constancy of chronic peritoneal dialysis patients includetotal protein, albumin, glucose, creatinine, urea, sodium, and chlorine.The manner in which the concentration of these monitored solutes in thepatient's blood changes during the 24-hour testing period was noted.

The results of the measurements are shown in FIG. 3, which shows thechange over time in the total protein and albumin (colloid)concentration in the blood. In FIG. 3, the solid black circles ●indicate the concentration of total protein in the blood and the solidblack diamonds ♦ indicate the concentration of albumin in the blood. Itis clear from FIG. 3 that very little change in the total proteinconcentration and the albumin concentration in the blood was observedover the 24 hour period of the test.

FIG. 4 shows the change over test time in the concentration of glucose,creatinine, and urea (crystalloids) in the blood. In FIG. 4, the solidblack circles ● indicate the concentration of creatinine in the blood,the solid black diamonds ♦ indicate the concentration of urea in theblood, and the solid black triangles ▴ indicate the concentration ofglucose in the blood. As can be understood from FIG. 4, very littlechange in the creatinine and urea concentration in the blood wasobserved over the 24-hour period of the test. Also, although theconcentration of glucose in the blood rose during testing, hardly anychange was observed between that at the start and that at the end oftesting.

FIG. 5 shows the change in blood concentration of sodium and chlorine(electrolytes) during testing. In FIG. 5, the solid black circles ●indicate the concentration of sodium in the blood and the solid blackdiamonds ♦ indicate the concentration of chlorine in the blood. It isclear from FIG. 5 that very little change in the concentration of sodiumand chlorine in the blood was observed over the 24-hour test period.

From the above it is clear that there is very little change in the bloodconcentration of all of the monitored solutes, these being totalprotein, albumin, glucose, creatinine, urea, sodium, and chlorine, whichare regarded as the monitored solutes that are important for confirmingthe constancy of chronic peritoneal dialysis patients, between that atthe start of testing and that after the 24-hour test period.Consequently, it is conceivable that obtaining a blood and urine sampleonly once either at the start of testing or after the 24-hour testperiod would be sufficient.

Here, in consideration of patient convenience, it is necessary to take ablood sample and perform the peritoneal equilibrium test (PET) at ahospital, and ultimately to submit the samples of drained dialysis fluidto the hospital. Taking this into consideration, when a blood sample istaken and the PET test is performed at the start of testing, the patientis required to travel to the hospital twice, and this is not preferable.On the other hand, because the storage of drained dialysis fluid ispossible at home, if the patient were to bring drained dialysis fluidsamples to the hospital and have blood drawn after testing is finished,it would not be necessary for the patient to be admitted to thehospital. Consequently, as shown in FIG. 2, if the blood and urinesamples 22, 24 are obtained and the PET is performed in the hospitalwhen the test sequence has finished, then by the patient coming to thehospital only a single time on the final day, all of the tests can beperformed. Thus, the patient is freed from time constraints and themental and economic burden on the patient can be reduced.

It should be noted that, as shown in FIG. 3, there is an experimentallyclear positive correlation between the albumin concentration of thedrain fluid and the total protein concentration of the drain fluid.Consequently, the albumin concentration of the drain fluid, which isexpensive to measure, can be extrapolated using the total proteinconcentration of the drained fluid, which is inexpensive to measure. Inother words, by measuring only the total protein concentration of thedrain fluid and calculating the albumin concentration of the drain fluidwithout actually measuring it, the test results can be obtained.

With the testing method according to this embodiment, it is possible tocollect the water removal amount and the solute concentration of thedrain fluid as temporally discontinuous clinical data on the low osmoticpressure fluid and the medium osmotic pressure fluid. FIG. 6 and FIG. 7respectively show an example of the data on the water removal amount(corresponding to amount of abdominal cavity dialysis fluid) and thesolute concentration of the drain fluid that are collected using thistesting method, plotted against dwell time. In FIG. 6, the solid blackcircles ● indicate the amount of abdominal cavity dialysis fluid in thecase of the dialysis fluid having a high osmotic pressure (mediumosmotic pressure fluid) and the solid black diamonds ♦ indicate theamount of abdominal cavity dialysis fluid in the case of the dialysisfluid having a low osmotic pressure (low osmotic pressure fluid). InFIG. 7, the solid black circles ● indicate the solute concentration inthe case of the dialysis fluid having a high osmotic pressure (mediumosmotic pressure fluid), the solid black diamonds ♦ indicate the soluteconcentration in the case of the dialysis fluid having a low osmoticpressure (low osmotic pressure fluid), and the thick solid lines eachindicate the solute concentration of the blood.

With the testing method of the present embodiment, clinical data arecollected for dwell times of three different lengths, and dialysisfluids with different osmotic pressures are infused in alternation. Thisis to prevent excessive water removal before it occurs by continuouslyusing dialysis fluid having high osmotic pressure. Consequently, inaccordance with more specific conditions, the infusion of low osmoticpressure fluid can be partially continuous, but the low osmotic pressurefluid and the medium osmotic pressure fluid are infused in alternationso that the infusion of medium osmotic fluid is not continuous.According to these conditions, in the procedure shown in FIG. 2, it ispossible to switch the (12:30) infusion of low osmotic pressure fluid(360) and the (15:30) infusion of medium osmotic pressure fluid (400).

Also, in the present embodiment, at the end of the step of alternatelyrepeating the infusion of dialysis fluids having different osmoticpressures, that is, when the peritoneal equilibrium test is started, thedialysis fluid with the relatively higher osmotic pressure is infused.This is because for the peritoneal equilibrium test it is necessary toinfuse the dialysis fluid having the higher osmotic pressure. The reasonfor this is as follows. In patients with advanced peritoneumpermeability, there is little hope that sufficient water removal willoccur with the peritoneal dialysis fluid having the lower osmoticpressure. Consequently, with relatively short (for example, four hours)dwell times, the amount of urine toxin that is removed reaches theremoval limit, and accurate test values cannot be obtained. On the otherhand, with the dialysis fluid having the higher osmotic pressure, theurine toxin removal limit is higher than that of the dialysis fluidhaving the lower osmotic pressure. For this reason, the removal limit isnot reached in a short dwell time, even for patients with advancedperitoneum permeability. Consequently, if the dialysis fluid having thehigher osmotic pressure is used, then accurate test values can beobtained regardless of the patient's peritoneum permeability. Thus, itis preferable that the dialysis fluid having the higher osmotic pressureis infused last in the step of alternately repeating fluid infusion andfluid drain.

Also, in this embodiment, the dialysis fluid having the higher osmoticpressure is infused first in the step of alternately repeating theinfusion of dialysis fluids having different osmotic pressures. This isbecause a long dwell time can be secured if the dialysis fluid havingthe higher osmotic pressure is infused, and this is suited for startingthe step of repeated fluid infusion in the evening. By contrast, thedwell time is short when the dialysis fluid having the lower osmoticpressure is infused, and this requires fluid infusion and drain to becarried out at short intervals and affects the lifestyle of the patient.Thus, it is preferable that the dialysis fluid having the higher osmoticpressure is infused first in the step of repeating fluid infusion andfluid drain.

As illustrated above, the present embodiment achieves a simple testingmethod that uses test data from a single blood sample taken at arepresentative time during a 24-hour period, without substantiallyaffecting the precision of analysis by computer simulation, based on thefinding that there is very little change in the blood soluteconcentration in chronic peritoneal dialysis patients over a 24-hourtest period. As a result, the feeling of time confinement and theeconomic and mental burden that the test imposes on patients can bereduced.

Also, by taking a blood sample only once during testing, preferably whentesting is finished, along with a peritoneal equilibrium test (PET),which is a qualitative evaluation method, it is possible to minimize theamount of time spent in the hospital for the purpose of testing.

INDUSTRIAL APPLICABILITY

The method for testing peritoneal function of the present inventionachieves a simple testing method that uses test data from a single bloodsample taken at a representative time during a 24-hour period, withoutsubstantially affecting the analysis precision of the computersimulation. As a result, it is possible to reduce the feeling of timeconfinement and the economic and mental burden that the test imposes onpatients.

1. A method for testing peritoneal function in order to evaluate thecondition of a peritoneal dialysis patient, comprising the steps of:alternately and repeatedly infusing and draining with a first peritonealdialysis fluid having a first osmotic pressure and a second peritonealdialysis fluid having an osmotic pressure lower than the first osmoticpressure; analyzing the drain fluid in order to assess both the amountof the peritoneal dialysis fluid that is retained within the abdominalcavity of a patient, and the concentration of monitored solutes in theperitoneal dialysis fluid for each time of the fluid drain; performing aperitoneal equilibrium test, by infusing a dialysis fluid, repeating forpredetermined times and at predetermined time intervals draining thedialysis fluid, sampling some of the drained fluid, returning thedrained fluid to the patient, and then draining the dialysis fluid; andperforming a blood test in order to assess concentrations of themonitored solutes; wherein the fluid infusion and the fluid drain isperformed at least three times for each of the dialysis fluids of therespective osmotic pressure, a dwell time from when the dialysis fluidis infused until when the dialysis fluid is drained being set to bedifferent each time when using dialysis fluid having the same osmoticpressure, the repetition of the fluid infusion and the fluid drain isperformed in the order such that the dialysis fluid of the higherosmotic pressure is used for the first and the last times, the step ofperforming the blood test is executed only once; and the peritonealequilibrium test is performed last of all the steps, and the blood testis performed immediately before the peritoneal equilibrium test, or isperformed during the peritoneal equilibrium test.
 2. The method fortesting peritoneal function according to claim 1, wherein the monitoredsolutes for assessing peritoneal function are total protein, albumin,glucose, creatinine, urea, sodium, and chlorine.
 3. The method fortesting peritoneal function according to claim 2, wherein the albuminconcentration of the drain fluid is extrapolated based on the totalprotein concentration of the drain fluid.